After the local treatment of the primary tumor (protonbeam-therapy, enucleation, external radiotherapy) patients with high risk of metastasis are randomized between: * Adjuvant chemotherapy with Fotemustin. * Observation Both groups are followed during 3 years for Metastasis- Free Survival, safety and tolerance of Fotemustin, quality of life, and Overall Survival.
High risk uveal melanoma is defined by : * Clinical criteria: Largest Tumor Diameter ≥ 15 mm with extra scleral extension and/or retinal detachment or Largest Tumor Diameter ≥ 18 mm AND/ OR * Genomic high risk signature (aCGH +/-LOH): Monosomy 3 or partial deletion of 3p associated with any 8 gain. Treatment schedule : * Induction: Fotemustin 100 mg/m², D1-D8-D15, 1 hour IV infusion, 1 cycle * Maintenance : restart on D50, Fotemustine : 100 mg/m², 1 hour IV infusion, D1 D21, 5 cycles. Both groups are followed during 3 years for Metastasis- Free Survival, safety and tolerance of Fotemustin, quality of life, and Overall Survival. Note :Based on the second interim analysis showing futility, and no chance to observe any significant statistical difference at the end of the study, the Independent Data Monitoring Committee recommended to stop randomization and amend the protocol to propose an interventional surveillance to high-risk patients as per protocol (April 2016).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
302
Fotemustin is given for 6 cycles : * One Induction cycle: Fotemustin 100 mg/m², 1 hour IV infusion, D1D8D15, 5 week rest period, restart on D50. * Five Maintenance cycles: Fotemustin 100 mg/m², 1 hour IV infusion, D1-D21.
Intensive surveillance * Total duration: 3 years. * liver functional tests/3 months, - liver MRI or CT-scan/6 months, - whole body CT-scan/12 months.
Centre Jean Perrin
Clermont-Ferrand, France
Centre Léon Bérard
Lyon, France
CHU Nice
Nice, France
Centre Antoine Lacassagne
Nice, France
Institut Curie
Metastasis-Free survival
Time between patient randomization and metastases occurrence or death
Time frame: 3 years
Overall Survival
Time between patient randomization and death
Time frame: 3 years
Safety : incidence of Adverse Events and Serious Adverse Events and laboratory abnormalities
using National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) V3
Time frame: 3 years
Quality of life assessment
Using QLQ-C30 questionary.
Time frame: Baseline, 6 months and 3 years
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Paris, France
Centre Hospitalier Universitaire Vaudois
Lausanne, Switzerland